It is a privilege to witness a revolution in thinking in Biology, but that is surely what we have seen in the past few years in our understanding of the roles of mitochondria in cell biology. Ten years ago, it all seemed simple: the mitochondrion was ‘the powerhouse of the cell’, the cliche of every biology text-book. Chemiosmotic principles were solved, the mechanism of ATP synthesis was understood at the molecular level.1 What more could there be? And yet now we know otherwise – mitochondria are intimately involved in the delicate processes that sustain the balance between cell life and cell death. And of course, as the problem becomes the focus of attention in ever more laboratories, so new and surprising observations emerge. For some years, the proposal that mitochondria might play a central role in apoptotic cell death was thought improbable, despite the observation that Bcl-2, that exemplar anti-apoptotic protein, was localised to the mitochondrial outer membrane.2 Since the cluster of publications emerged in 1994–1995 showing that cytochrome c (cyt c), that most innocuous of pink proteins, is a key initiator of apoptotic cell death (for an unusual review, see http://www.ergito.com/gtexpts/wang.htm), the mitochondrion has moved centre stage and has become the focus of research in many labs worldwide.

Perhaps, in the midst of all this activity, it is worth remembering that cell death in many disease processes is not apoptotic but necrotic, or perhaps some amalgam of the processes. There seems to be a tendency to regard necrotic cell death as boring – the inevitable consequence of energetic failure. However, there still must be a point of no return, and many intriguing questions remain. What defines the degree of energetic failure that can be tolerated and that which will inevitably proceed to cell death? Why do we have 3 min to start resuscitation at a cardiac arrest? What happens that makes the loss of function – signalled in the brain by a loss of consciousness – irreversible?

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